SEMIPREPARATIVE ENANTIOMERIC SEPARATION OF A SERIES OF PUTATIVE MELATONIN RECEPTOR AGENTS USING TRI-ACETYLCELLULOSE AS CHIRAL STATIONARY-PHASE

In order to obtain milligram amounts of the enantiomers of a series of compounds to be tested for binding to the melatonin binding site, a s ystem for semipreparative enantiomeric separation was set up using tri -acetylcellulose as the chiral stationary phase. Interactions of this class of compounds with tri-acetylcellulose were examined on an analyt ical scale with a series of 20 compounds. Apparently, both steric and electrostatic interactions determine retention behavior on tri-acetylc ellulose. Semipreparative separations were carried out for a subset of seven compounds. The purity of the first eluting enantiomer usually w as around 99%, whereas the purity of the second eluting enantiomer was slightly less. The system described is easy to use and has the major advantage that a series of compounds can be separated with one techniq ue. The purities obtained are sufficient for a first screen of their a ffinity. (C) 1994 Wiley-Liss, Inc.